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Scientists characterize proteome of human cornea

02.08.2005

An international group of researchers has characterized the proteome of the human cornea. In doing so, they have identified 141 distinct proteins, 99 of which had not been previously recognized in mammalian corneas. The details of their findings appear in the August/September issue of Molecular and Cellular Proteomics, an American Society for Biochemistry and Molecular Biology journal.

The cornea is the transparent, dome-shaped window that covers the front of the eye. Although it is clear and seems to lack substance, the cornea is actually a highly organized group of cells and proteins. Its functions include shielding the eye from germs, dust, UV light, and other harmful matter and acting as the eyes outermost lens.

Approximately 120 million people in the United States wear eyeglasses or contact lenses to correct nearsightedness, farsightedness, or astigmatism. These vision disorders are often the result of incorrect curvature or irregular shape of the cornea and are the most common vision disorders in this country. Other diseases that affect the cornea range from bacterial, fungal, and viral infections (keratitis) and allergies to various dystrophies including keratoconus.

"Corneal damage and disorders account for several million cases of impaired vision and are second to cataracts as the most important cause of blindness in the world," explains study author Dr. Jan J. Enghild of the University of Aarhus in Denmark. "Corneal infections by bacteria, fungi, or viruses are common disorders that can lead to corneal opacification. A group of inherited corneal disorders including granular and lattice corneal dystrophies are characterized by deposition of insoluble and opaque macromolecules in the cornea. Other disorders associated with loss of corneal transparency arise from cornea swelling (Fuchs dystrophy) or thinning and change of curvature of the cornea (keratoconus)."

In order to learn more about the cornea and corneal disorders, Dr. Enghild and colleagues characterized the most abundant proteins found in the non-diseased human cornea. They identified 141 distinct proteins, 70% of which have not previously been identified in the cornea. This work is the most comprehensive protein study of the cornea to date.

"Surprisingly, about 15% of the identified proteins in the cornea are classical blood proteins, which indicate that they originate from the blood stream around the cornea and are not produced in the cornea," notes Dr. Enghild. "Our results also showed that proteolysis and post-translational modifications of proteins are common events in the normal human cornea."

Among the molecules that the scientists identified were proteins involved in antimicrobial defense, heme and iron transport, tissue protection against UV-radiation and oxidative stress. Several other proteins were known antiangiogenic factors, which prevent the formation of blood vessels.

The results from this research may open the door to future therapeutics for a myriad of corneal disorders. "It is essential to know the biochemical composition of normal healthy corneas in the effort to understand the molecular mechanisms behind corneal disorders," emphasizes Dr. Enghild. "By comparative proteomic studies of diseased and normal corneas we can identify differences in the expression profiles that may suggest avenues for therapeutic interventions. Because the cornea is so accessible, the potential for developing effective drugs for the treatment of corneal diseases is good. Furthermore, the work is likely to improve the clinical classifications of corneal diseases. Identification of the protein profile of the normal human cornea may also be very useful in the effort toward generating artificial corneas for transplantation."

To follow up on their initial research, Dr. Enghild and his colleagues have begun proteomic studies of corneas affected by granular and lattice corneal dystrophies, and are also planning on looking at other cornea diseases such as keratoconus and Fuchs dystrophy.

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